title: The T-cell oncogene Tal2 Is a Target of PU.1 and upregulated during osteoclastogenesis.
abstract: Transcription factors play a crucial role in regulating differentiation processes during human life and are important in disease. The basic helix-loop-helix transcription factors Tal1 and Lyl1 play a major role in the regulation of gene expression in the hematopoietic system and are involved in human leukemia. Tal2, which belongs to the same family of transcription factors as Tal1 and Lyl1, is also involved in human leukaemia. However, little is known regarding the expression and regulation of Tal2 in hematopoietic cells. Here we show that Tal2 is expressed in hematopoietic cells of the myeloid lineage. Interestingly, we found that usage of the Tal2 promoter is different in human and mouse cells. Two promoters, hP1 and hP2 drive Tal2 expression in human erythroleukemia K562 cells, however in mouse RAW cells only the mP1 promoter is used. Furthermore, we found that Tal2 expression is upregulated during oesteoclastogenesis. We show that Tal2 is a direct target gene of the myeloid transcription factor PU.1, which is a key transcription factor for osteoclast gene expression. Strikingly, PU.1 binding to the P1 promoter is conserved between mouse and human, but PU.1 binding to P2 was only detected in human K562 cells. Additionally, we provide evidence that Tal2 influences the expression of the osteoclastic differentiation gene TRACP. These findings provide novel insight into the expression control of Tal2 in hematopoietic cells and reveal a function of Tal2 as a regulator of gene expression during osteoclast differentiation.
authors.affiliation: Georg-Speyer-Haus, Institute for Biomedical Research, Frankfurt, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Courtial
authors.forename: Christian
authors.initials: C
authors.lastname: Mücke
authors.forename: Stefanie
authors.initials: S
authors.lastname: Herkt
authors.forename: Stephan
authors.initials: S
authors.lastname: Kolodziej
authors.forename: Helge
authors.initials: H
authors.lastname: Hussong
authors.forename: Jörn
authors.initials: J
authors.lastname: Lausen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry / Q000235:genetics*; D002460:Cell Line; D017124:Conserved Sequence; D056426:Genetic Loci / Q000235:genetics; D023281:Genomics; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics*; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D053245:RANK Ligand / Q000494:pharmacology*; D013045:Species Specificity; D015534:Trans-Activators / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D016173:Macrophage Colony-Stimulating Factor; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D053245:RANK Ligand; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C086540:TAL2 protein, human